Dysregulation of stress responses in juvenile VPA rats: insights into autonomic and behavioral reactivity in Autism Spectrum Disorder

Abstract

An effective response to environmental challenges is essential for human survival, and child development plays a crucial role in shaping appropriate adult behaviors through the integration of sensory information, internal states (such as hunger and pain), past experiences, and future anticipations. Stress disorders, marked by excessive worry and fear, are commonly observed among individuals with Autism Spectrum Disorder (ASD). Rats prenatally exposed to valproic acid (VPA) are used as a model for ASD. To investigate possible changes in ASD stress systems, this study evaluated the autonomic and behavioral responses to tactile, nociceptive, and social stimuli in juvenile VPA-treated rats. Our results demonstrate a complex dysregulation of stress responses in VPAtreated rats. Chapter 1 revealed that VPA-treated rats display autonomic system dysregulation, increased susceptibility, and impaired habituation to mild tactile stress, similar to patterns in children with ASD, suggesting the model's usefulness for studying autonomic reactivity and stress susceptibility in humans. Chapter 2 found that VPAtreated rats exhibit similar but delayed behavioral responses to painful stimuli compared to control rats, indicating greater resilience of VPA-treated rats to this type of stress. In contrast, Chapter 3 show that VPA-treated rats displayed faster and more sustained freezing behavior under social stress, with a habituation deficit, aligning with social challenges in ASD. These results highlight VPA-treated rats' increased overall susceptibility to innocuous stress-inducing stimuli and significant habituation deficits, but slower responses to nociceptive stimuli, illustrating the complexity of stress responses. Our study validate the utility of the VPA rat model for understanding and leading to the development of treatments for ASD-related stress reactivity.